Vit D Deficiency in Adolescents

Vit D Deficiency in Adolescents Ashraf T Soliman MD PhD FRCP Rania Elalaily MSc Ped

High Prevalence of VDD in Adolescents (65%) 

In the 100 adolescents randomly selected from schools 65% of them have VDD ( 25OHD < 10 ng/ml) Soliman AT. J Trop Pediatr (2010) doi: 10.1093/tropej/fmq028

Significant predictors for VDD 

Limited exposure to sunlight

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Low oral intake of vitamin D

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Low physical activity Bener A, Al-Ali M, Hoffmann GF. Minerva Pediatr. 2009 Feb;61(1):15-22.

PRESENTATION OF VDD ADOLESCENTS VS CHILDREN Clinical Data  Biochemical Data  Radiological Data 

Soliman AT. J Trop Pediatr (2010) doi: 10.1093/tropej/fmq028

Clinical Manifestation of VDD in adolescents 

Pain in weight bearing joints, back, thighs, and calves ( 32/40)

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Difficulty walking and/or climbing stairs and/or running (9/40)

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Muscle cramps and/or facial twitches and/or carpopedal spasms (16/40)

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Genu valgus (3/40)

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Tetany (1/40) Disappearance or improvement of these symptoms were achieved in the majority (37/40) of these patients 3 months after the injection.

2. Biochemistry & Hormones

Ashraf Soliman MD PhD FRCP

Adolescent vs Children with VDD Children VDD

Adolescents- VDD

2.1

2.1

PO4 (mmol/L)

1.1**

1.4

ALP (U/L)

769**

404

6.7

9.3

249**

123

Ca (mmol/L)

25OHD (ng/ml) PTH (pg/ml)

Before treatment 

25 OH D and Ca concentrations did not differ among the 2 groups.

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Serum PO4 concentration was significantly lower in children vs adolescents

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PTH and ALP concentrations higher in children vs adolescents

This reflects slower rate of growth and/or better adaptation (larger bone mass) in adolescents.

Biochemical data after 3 months of treatment Children

Adolescents

Ca (mmol/L)

2.3

2.3

PO4 (mmol/L)

1.65

1.7

ALP (U/L)

404

196

25OHD (ng/ml)

28.5

27

35

34

PTH (pg/ml)

IGF-1 (ng/ml)

IGF-I Before vs After treatment 200 180 160 140 120 100 80 60 40 20 0

Before 3-D Column 2 After

Adolescents

Children

Three months after injecting vitamin D 

Serum 25 OH D, Ca and PO4 concentrations increased significantly in the 2 groups and ALP and PTH concentrations significantly decreased.



ALP concentrations were still significantly higher in infants vs adolescents (reflecting rapid growth ( IGF-I)

VIT-D Vs IGF-I

Response to Treatment

In adolescents with VDD 

An IM mega dose of vitamin D increased serum 25OHD levels to normal level ( > 20 ng/ml) (37/40) for 3 months.

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Correction of serum PTH,ALP,Ca, PO4 and increased IGF-I concentrations.

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Symptoms related to VDD in adolescents disappeared in the majority of patients after 4-6 weeks of the injection Serum creatinine remained normal in all participants

Duration of Action of The Megadose 6 months after injecting mega dose 

39/40 adolescents had 25OHD level < 20 ng/ml).



Only 1 adolescent and 3 children had 25 OH D = or above 20 ng/dl.

Serum 25 OH D in NT adolescents with vitamin D deficiency after vit D injection 50 45

25 OH D ng/ml

40 35 30 25 20 15 10 5 0 0

3 months

6

An IM mega dose of cholecalciferol is an effective therapy for treatment of hypovitaminosis D in children and adolescents for 3 months but not enough for 6 months.


3. Radiological Data

Adaptation to vitamin D deficiency 

1. Increased PTH stimulates 1 alpha hydroxylation of vitamin D---- more calcium absorption from the gut.

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2. low IGF-I decelerates linear growth and decreases Calcium use in bones.

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3. Low IGF-I permits the catabolic action of PTH on the bone to maintain serum calcium level.

Adaptation Theory Decreased circulating and locally produced IGF-I in rachitic children appears to be an adaptive process to inhibit linear growth (in growth plate) and bone mineral accretion (diaphysis) during vitamin D deficiency to keep normocalcemia.

Adaptation Adolescents Vs Children with VDD Adolescents are better adapted: 1. 2. 3. 4.

less symptomatic clinically lower incidence of low PO4 and Ca Lower increase of PTH and ALP Lesser radiological manifestations  Large bone mass (CaPO4 store)  Less requirement for calcium and PO4 /kg (slower growth rate than infants) Soliman AT. J Trop Pediatr (2010) doi: 10.1093/tropej/fmq028

Fig 1: Pattern (I) Adolescent Vitamin DD Rickets : The lesions appear as multilocular bone cystic lesion with sclerotic margins , exocentric subcortical location with no cortical erosions, no periosteal reaction , no osteoporosis , no other metaphyseal manifestations of VDDR. The lesions may simulate non-ossifying fibroma but mostly it simulates brown tumor secondary to hyperparathyroidism.

Fig 2 : Pattern (II) Adolescent Vitamin DD Rickets

Generalized diminished bone density with prominent primary and 2ry bone trabeculation , Wide metaphyseal zone of relatively more lucency with rather loss of bone trabiculation representing wide metaphyseal zone of poor ossification of bone matrix 2ry to rachitic changes , No cupping or fraying of metaphyses identified

Fig 3 : Severe Pattern (II) Adolescent Vitamin DD Rickets ; Plain X ray hand and wrist , Pelvis demonstrating; generalized diminished bone density with prominent 1ry bone trabiculation , hazy apophysis of ischial bone and iliac crest , no other metaphyseal changes , no bony cystic changes

Clinical Observation Type I pattern occurs with   

Obese or overweight Normal intake of milk (CaPO4) Normal IGF-I and high PTH

Type II pattern occurs with   

Underweight No or low intake of milk (CaPO4) Low IGF-I and high PTH


Effect of treatment on radiological changes Soliman AT. J Trop Pediatr (2010) doi: 10.1093/tropej/fmq028

A&B

Fig. 4 Patient with adolescent Vit.DDR manifested with pattern I ( multilocular cystic lesion) A&B before treatment , C&D after 6 months from treatment with mega dose of Vit D , there is marked improvement of the cyst with recalcification of the sub cortical part of the lesion, marked regression of the number of loculi denoting good response to treatment. C&D

Plain Films at Presentation

Metaphyseal osteoporosis Prom. Primary striations 2ry Hypo PO4

Before Vs after Vit D (6 months) Metaphyseal osteoporosis Prom. Primary striations

12 Months after Vit D Marked resolution of the cyst with mild persistence of the linear trabecular pattern of the metaphysis

Vitamin D deficiency Why Adolescents are more adapted than Children

ADAPTATION to VDD 1.

Bone Mass (Height, Weight)

2.

IGF-I

Adaptation in Adolescents vs Children (height) 1.

Increased bone mineral content with growth in stature gives more calcium stores available for adaptation

Bone mineral content/bone area C. Molgaard Arch Dis Child. 1997 76(1): 9–15.

Adaptation in Adolescents vs Children (Weight) 

In adolescent females, the total bone mass increases when both absolute FM and percentage of FM increase.

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The association between total bone mass content TBMC and fat mass (FM) is not linked to age or skeletal structure. The mechanism may be :

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1) an increment in estrogen production in girls with more FM; 2) a mechanical effect on skeletal structure because of excess weight;

Association of Fat Mass with Bone Mineral Content in Female Adolescents. Obesity Research (2002) 10, 715

Adaptation in Adolescents (IGF-I) High IGF-I in obese vs non obese

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Serum IGF-I level is significantly higher in simple obese vs non-obese adolescents matched for pubertal stage Endocr J. 1998 Apr;45(2):221-7 Hormone research 1991; 36, No. 5-6

IGF-I and BMC 

In children IGF-I is a determinant of longitudinal bone growth and acquisition of bone mass,

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In adults IGF-I is important in the maintenance of bone mass.

Endocrine Reviews 2008, 29: 535–559 J Clin Endocrinol Metab. 2002, ;87(6):2883

Even in sunny climates 

Adolescence is a critical period of skeletal mineralisation, (>35% of the peak bone mass (PBM)of a mature adult during 4 y surrounding the peak pubertal growth spurt) (Adolescents can be at risk of rickets)

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Adolescents with VDD who attain a lower PBM at maturity have a higher risk of osteoporosis and fractures in later life.

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Limb and joint (knee, ankle, hip) pains and myopathy were the most common presenting symptoms.

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Radiological evidence was present in some cases.

Recommendation

Vitamin D supplement to adolescents who have limited exposure to sunshine for environmental, cultural and /or religious reasons.

Thank you

SECONDARY CAUSES OF OSTEOPOROSIS Patients with at least 1 new diagnosis (n=84) Vitamin D deficiency,